Protective Effect of Liuwei Dihuangwan on Mitochondrial Damage in AD Model of Caenorhabditis Elegans / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） 1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

The value of CT for differentiating gastric leiomyoma from gastric schwannoma / 中国医师进修杂志

Objective:To evaluate the value of CT for differentiating gastric leiomyoma (GLM) from gastric schwannoma (GS).Methods:The clinical and imaging data of 42 patients with GLM (GLM group) and 41 patients with GS (GS group) were analyzed retrospectively. The general information and CT features were compared between two groups. The independent factors for differentiating GLM from GS were obtained by multivariate Logistic regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficiency of the model.Results:The proportion of female and age in GLM group were significantly lower than those in GS group: 59.52% (25/42) vs. 85.37% (35/41), (51.83 ± 10.52) years old vs. (58.80 ± 10.63) years old, and there were statistical differences ( P<0.01). The upper part of the stomach rate, irregular shape rate, intraluminal growth rate, ratio of long diameter to short diameter and mild to moderate enhancement rate in GLM group were significantly higher than those in GS group: 71.43% (30/42) vs. 14.63% (6/41), 52.38% (22/42) vs. 21.95% (9/41), 92.86% (39/42) vs. 19.51% (8/41), 1.90 ± 0.55 vs. 1.34 ± 0.28 and 92.86% (39/42) vs. 51.22% (21/41), the cystic degeneration rate, ulcer rate, incidence of tumor-associated lymph node, CT values of venous phase and delayed phase in GLM group were significantly lower than those in GS group: 2.38% (1/42) vs. 26.83% (11/41), 7.14% (3/42) vs. 24.39% (10/41), 2.38% (1/42) vs. 60.98% (25/41), (59.21 ± 9.75) HU vs. (66.22 ± 10.33) HU and (65.02 ± 8.62) HU vs. (76.85 ± 11.89) HU, and there were statistical differences ( P<0.01 or <0.05); there were no statistical difference in the rate of calcification and the CT values of plain scan and arterial phase between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the tumor location, growth mode, tumor-associated lymph node and ratio of long diameter to short diameter were the independent factors for differentiating GLM from GS ( OR = 34.385, 25.314, 0.023 and 97.700; 95% CI 2.848 to 415.171, 2.674 to 239.670, 0.001 to 0.637 and 3.113 to 3 066.549; P<0.01 or <0.05); when the model threshold was >0.647, the area under the curve was 0.988 (95% CI 0.934 to 1.000), with a sensitivity of 92.9% and specificity of 97.6%. Conclusions:When the tumor is prone to the upper part of the stomach, intraluminal growth, ratio of long diameter to short diameter >1.28, and the absence of the tumor-associated lymph node, GLM tends to be considered, on the contrary, it tends to be GS. Therefore, CT imaging features have certain value in differentiating GLM from GS before surgery.

Surgical treatment for perihilar cholangiocarcinoma:a single-center experience / 中华外科杂志

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.

Progress in perioperative management of ABO-incompatible pediatric liver transplantation / 中华外科杂志

ABO incompatible(ABO-I) liver grafts will affect the prognosis of liver transplantation. With the improvement of perioperative treatment,including plasma exchange,rituximab,splenectomy,etc.,the prognosis of ABO-I liver transplantation has been greatly improved. Because children's immune systems are not fully developed,the perioperative management of ABO-I pediatric liver transplantation is significantly different from that of adults. Reducing the perioperative anti-donor ABO antibody titer is the key to the perioperative management of ABO-I liver transplantation. This article summarizes literatures on the perioperative management of ABO-I pediatric liver transplantation, including the perioperative anti-rejection regimen in pediatric recipients of different ages, splenectomy, postoperative monitoring and postoperative complications, etc.

Mechanism of tonifying Qi by traditional Chinese medicine from mitochondrial dynamics / 中国中药杂志

According to the traditional Chinese medicine(TCM) theory, Qi is the essential component maintaining life. Mitochondria are the cellular organelles that generate energy. Qi exhibits abundant common characteristics in bioenergetics compared with mitochondria which control the cellular energy through fusion and fission. Studies have proven that the qi-tonifying function of Chinese medicinal plants and their components facilitates mitochondrial fusion, therefore enhancing ATP synthesis. These studies provide a framework for deciphering the pharmacological mechanisms of Qi-tonifying herbs. This article introduces the common source and function shared by Qi and mitochondria and the regulatory effects of herbal remedies on energy from mitochondria dynamics. This review aims to interpret the connotation of tonifying qi in TCM theory based on the modern biomedical theory.

Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment / 中国中药杂志

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

Design and development of a multifunctional moxibustion treatment machine based on heat-sensitive moxibustion therapy / 中国针灸

A multifunctional moxibustion treatment machine is designed and developed to assist the heat-sensitive moxibustion therapy. Through the motion control of the stepping motor by programmable logic controller (PLC), the automatic control is obtained for the acupoint detection of heat-sensitive moxibustion therapy and the manual operation of moxibustion. The skin temperature is monitored in real-time, using infrared non-contact temperature measurement technology. Based on the deviation of the temperature set value and the monitoring one, the distance between the moxibustion device and the exerted region is adjusted automatically by PLC so that the temperature is controlled practically. The multifunctional moxibustion treatment machine based on the heat-sensitive moxibustion therapy is capable of the operation control of mild moxibustion, circling moxibustion, sparrow-pecking moxibustion and along-meridian moxibustion techniques, as well as real-time monitoring of skin temperature. The temperature change curve of this machine is coincident with that obtained by the manual operation of heat-sensitive moxibustion. This multifunctional moxibustion treatment machine assists the delivery of heat-sensitive moxibustion therapy and it is satisfactory in temperature control and precise in operation.

Label-free target discovery technology of small molecule drug and its application in traditional Chinese medicines / 药学学报

The discovery of drug targets plays a crucial role in drug research. Accurate information of small molecule drug-protein interaction can be provided by label-free target discovery technology without any structural modification at the small molecule. So, the label-free drug target discovery technology had become the powerful tool to discover the targets of drugs. Due to the “multi-component and multi-target” characteristics of traditional Chinese medicines (TCMs), the research on its targets and mechanism had been restricted. Based on potential of the label-free target discovery technology in the research of TCMs, this paper summarized the label-free target discovery technology and its application in TCMs research. It will provide a reference for the discovery of targets of TCMs and a new view for promoting the modernization of TCMs.

Diagnosis and Treatment of Klebsiella Pneumoniae Combined with Enterobacter Cloacae in Lumbar Intervertebral Space Infection / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical diagnosis and treatment of rare primary lumbar intervertebral space infection with Klebsiella pneumoniae and Enterobacter cloacae， and provide clinical experience for the diagnosis and treatment of this rare spinal infection. MethodsAn elderly male patient with low back pain and numbness in the left lower extremity for more than 7 months， which aggravated for more than 1 week， was diagnosed with lumbar disc herniation after laboratory and imaging examinations. After admission， the symptoms became acutely aggravated， and re-examination of lumbar enhanced MRI showed local enhancement at the posterior edge of the L3/4 intervertebral space. The VAS score was 9 points， and the lumbar JOA score was 6 points. A posterior lumbar interbody fusion of L3-L5 was performed， and L3/4 intervertebral disc specimens were collected during the operation for bacterial culture. ResultsBacterial culture results showed Klebsiella pneumoniae and Enterobacter cloacae infection. The patient was treated with sensitive antibiotics for 6 weeks after the operation， and the patient was cured during the follow-up of half a year after the operation. ConclusionFor middle-aged and elderly patients with clinical manifestations of acute severe low back pain or lower extremity pain， the possibility of spinal infection should be considered when routine laboratory and imaging examinations suggest lumbar degenerative diseases.

Mechanism of famous classical formula Huaihua Powder in treatment of ulcerative colitis based on metabonomics / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1β in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.

Mediating effect of self-efficacy on self-management ability and self-management behavior in patients with type 2 diabetes mellitus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests.@*METHODS@#In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years.@*RESULTS@#In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect.@*CONCLUSION@#Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.

A prospective cohort study of long-term fasting blood glucose variability and risk of mortality in patients with type 2 diabetes / 中华流行病学杂志

Objective: To investigate the association between long-term fasting blood glucose (FPG) variability and all-cause mortality in patients with type 2 diabetes. Methods: A total of 7 174 type 2 diabetic patients included in National Basic Public Health Service Program in Changshu of Jiangsu Province were recruited as participants. Long-term glucose variability was assessed using standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) across FPG measurements at the more than three visits. Death information were mainly obtained from the death registry system in Jiangsu. Then Cox proportional hazards regression models were used to estimate the associations of four variability indicators and all-cause mortality's hazard ratios (HRs) and their 95%CIs. Results: Among 55 058.50 person-years of the follow-up, the mean follow-up time was 7.67 years, and 898 deaths occurred during the follow-up period. After adjustment, compared with T1 group, the Cox regression model showed that HRs of T3 group in SD, CV, ARV and VIM were 1.24 (95%CI: 1.03-1.49), 1.20 (95%CI: 1.01-1.43), 1.28 (95%CI: 1.07-1.55) and 1.20 (95%CI:1.01-1.41), respectively. HRs of per 1 SD higher SD, CV, ARV and VIM were 1.13 (95%CI: 1.06-1.21), 1.08 (95%CI: 1.01-1.15), 1.05 (95%CI: 1.00-1.12) and 1.09 (95%CI: 1.02-1.16) for all-cause mortality, respectively. In the stratified analysis, age, gender, hypoglycemic agent and insulin uses had no effect on the above associations (all P for interaction >0.05). Conclusion: Long-term FPG glycemic variability was positively associated with the risk of all-cause mortality in type 2 diabetes patients.

Incidence of chronic obstructive pulmonary disease and risk factors in the Suzhou cohort / 中华流行病学杂志

Objective: To understand the incidence of chronic obstructive pulmonary disease (COPD) in the Suzhou cohort, and explore the risk factors for the development of COPD in Suzhou, and provide a scientific basis for COPD prevention. Methods: This study was based on the China Kadoorie Biobank project in Wuzhong District, Suzhou. After excluding individuals with airflow obstruction and self-reported chronic bronchitis, emphysema, or pulmonary heart disease at baseline, 45 484 individuals were finally included in the analysis. Cox proportional risk models were used to analyze risk factors of COPD and calculate hazard ratios and 95% confidence interval (CI) in the Suzhou cohort. The effect modifications of smoking on the association between other risk factors and COPD were evaluated. Results: Complete follow-up was available through December 31, 2017. Participants were followed up for a median of 11.12 years, and 524 individuals were diagnosed with COPD during the follow-up period; the incidence was 105.54 per 100 000 person-years. Multivariate Cox proportional risk regression models showed that age (HR=3.78, 95%CI:3.32-4.30), former smoking (HR=2.00, 95%CI:1.24-3.22), current smoking (<10 cigarettes/day, HR=2.14, 95%CI:1.36-3.35;≥10 cigarettes/day, HR=2.69, 95%CI:1.60-4.54), history of respiratory disease (HR=2.08, 95%CI:1.33-3.26), daily sleep duration ≥10 hours (HR=1.41, 95%CI:1.02-1.95) were associated with increased risk of COPD. However, education level of primary school and above (primary or junior high school, HR=0.65, 95%CI:0.52-0.81; high school and above, HR=0.54, 95%CI:0.33-0.87), consuming fresh fruit daily (HR=0.59, 95%CI:0.42-0.83) and consuming spicy food weekly (HR=0.71, 95%CI:0.53-0.94) were associated with reduced risk of COPD. Conclusions: The incidence of COPD is low in Suzhou. Older age, smoking, history of respiratory disease, and long sleep duration were risk factors for the development of COPD in the Suzhou cohort.

Nimbolide targeting SIRT1 mitigates intervertebral disc degeneration by reprogramming cholesterol metabolism and inhibiting inflammatory signaling

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study / 中国结合医学杂志

OBJECTIVE@#To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism.@*METHODS@#Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines.@*RESULTS@#A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis.@*CONCLUSION@#Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Implications of different metastatic sites for thoracic radiation in extensive-stage small cell lung cancer / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of thoracic radiotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) with different metastatic sites.Methods:A retrospective analysis was performed among 830 ES-SCLC patients who were admitted to our hospital from 2010 to 2019. They all received the first-line chemotherapy and had no progression after chemotherapy. 341 patients of them received thoracic radiotherapy after chemotherapy. The main endpoint was overall survival. The Chi-square test was used to compare the categorical data including gender and age, etc. Univariate survival analysis was estimated by Kaplan-Meier method and the log-rank test was used to compare the survival curves between two groups. A multivariate prognostic analysis was made by the Cox proportional hazard model.Results:In all the patients, the overall survival (OS) was 12.4 months. The patients with thoracic radiotherapy had significantly higher OS than the patients without thoracic radiotherapy (15.2 months vs.10.8 months, P<0.001). Thoracic radiotherapy significantly improved the OS in patients without liver metastasis (16.0 months vs.11.4 months, P<0.001) in the oligometastatic patients. But for the oligometastatic patients with liver metastasis, the OS benefit was not significant (14.2 months vs. 10.6 months, P=0.072). For polymetastatic patients without liver metastasis, thoracic radiotherapy offered significant OS benefits (14.5 months vs.10.9 months, P<0.001), but for the polymetastatic patients with liver metastasis, the OS was not improved with thoracic radiotherapy (10.2 months vs.9.2 months, P=0.715). Conclusions:In ES-SCLC patients, thoracic radiotherapy provides significant OS benefits in patients with oligometastases ES-SCLC without liver metastasis and for the liver metastatic patients may also benefit from thoracic radiotherapy based on the effectiveness of chemotherapy. In patients with multiple metastases, thoracic radiotherapy only improves the OS in patients without liver metastasis, but does not improve the prognosis in patients with liver metastasis.

Study on key amino acids in E2 protein of recombinant side chain of dioxygate dehydrogenase complex in primary biliary cholangitis / 中华风湿病学杂志

Objective:To explore the key amino acids of side chain dioxate dehydrogenase complex E2 protein (BCOADC-E2) that can react specifically with specific autoantibody anti-mitochondrial antibodies (AMA)-M2 in patients with primary biliary cholangitis (PBC).Methods:The homologous target gene BCKD, which expressed the epitopes of BCOADC-E2 protein, was cloned and recombined with the engineering plasmid pGEX-4T1. Fifteen point mutant plasmids were obtained by polymerase chain reaction (PCR) and transferred to the prokaryotic expression strain for protein expression and purification. Fourteen mutant proteins and one wild-type protein were obtained. The AMA-M2 specificity of the 14 mutant proteins was measured by enzyme-linked immuno sorbent assay (ELISA), and the amino acids that were critical to the specificity of BCOADC-E2 and AMA-M2 were identified by comparing the specificity of the 14 mutant proteins with that of the wild type proteins. Differences between groups were analyzed by analysis of variance, LSD- t test. Results:A total of 14 mutant proteins and 1 wild-type protein were obtained.The specific reaction degree of mutant protein pGEX-BCKD-S1A (1.634±0.328) and pGEX-BCKD-C3A (1.744±0.345) with serum AMA-M2 in patients with PBC was higher than that of wild-type protein pGEX-BCKD (1.000±0.000) with AMA-M2; Mutant protein pGEX-BCKD-E4A (0.157±0.067), pGEX-BCKD-V5A (0.057±0.029), pGEX-BCKD-Q6A (0.580±0.166), pGEX-BCKD-S7A (0.744 ±0.125), pGEX-BCKD-D8A (0.351 ±0.135), pGEX-BCKD-S10A (0.496 ±0.158), pGEX-BCKD-V11A(0.149±0.089), pGEX-BCKD-T12A(0.061±0.043), pGEX-BCKD-I13A(0.007±0.017), pGEX-BCKD-T14A (0.198±0.101), pGEX-BCKD-S15A (0.156±0.087), The specific reaction degree of pGEX-BCKD-R16A (0.884±0.099) with AMA-M2 was lower than that of wild-type protein pGEX-BCKD (1.000±0.000) with AMA-M2.Conclusion:The cysteines at positions 1 and 3 of BCOADC-E2 protein were the key amino acids to improve the specific reaction between BCOADC-E2 and AMA-M2. The mutant proteins formed after amino acids at position 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15 and 16 are replaced by alanine can decrease the specificity of AMA-M2. Amino acids at positions 5 and 13 are the key amino acids that affect the specific reaction between BCOADC-E2 and AMA-M2, and have an important effect on the function of BCOADC-E2 protein.

The impact of whole brain radiation therapy on overall survival in patients with extensive stage small cell lung cancer with brain metastases / 中华放射肿瘤学杂志

Objective:To evaluate whether whole brain radiation therapy(WBRT) could benefit small cell lung cancer (SCLC) patients with brain metastases.Methods:Clinical data of 245 patients who were diagnosed with extensive stage SCLC with brain metastases admitted to our hospital from 2010 to 2020 were retrospectively analyzed. Among them, 168 patients received WRBT (WBRT group, radiation dose: 30Gy in 10 fractions), and 77 patients did not receive WBRT (non-WBRT group). All patients received 4-6 cycles of chemotherapy, and the chemotherapy regimen included cisplatin (or carboplatin) plus etoposide. One hundred and fifteen patients received thoracic radiotherapy. The endpoint was overall survival after brain metastases(BM-OS). Chi-square test was used to compare categorical data, and stabilized inverse probability of treatment weighting(sIPTW) was used to match the factors between WBRT and no-WBRT groups. Survival analysis was estimated by Kaplan-Meier method, and the log-rank test was used to compare survival curves between two groups. Results:The median BM-OS for the whole group of patients was 9.1 months, and 10.6 months and 6.7 months in the WBRT and non-WBRT groups, respectively( P=0.003). After balanced influencing factors with stabilized sIPTW, significant difference still existed in BM-OS between two groups( P=0.02). In 118 patients with synchronous brain metastases, the median BM-OS in two groups were 13.0 months and 9.6 months( P=0.007); and in 127 patients with metachronous brain metastases, the median BM-OS were 8.0 months and 4.1 months( P=0.003). In 50 patients without extracranial metastases, the median BM-OS were 13.3 months and 10.9 months( P=0.259)in two groups; while in 195 patients with extracranial metastases, the median BM-OS were 9.5 months and 5.9 months( P=0.009)in two groups. Conclusions:WBRT could prolong the OS in extensive stage SCLC patients with brain metastases.

Effect of Liangxue Jiedu decoction on intestinal flora in patients with hepatitis B virus-related acute-on-chronic liver failure: An analysis based on high-throughput sequencing / 临床肝胆病杂志

Objective To investigate the effect of Liangxue Jiedu decoction on intestinal flora in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods The patients who were hospitalized and diagnosed with HBV-ACLF in Beijing Ditan Hospital from October 2018 to October 2019 were enrolled, and healthy individuals were enrolled as HP group. High-throughput sequencing was used to screen for the differences in bacterial diversity and species between HBV-ACLF patients and healthy individuals, and differentially expressed bacteria between the two groups were screened out at the phylum and genus levels. With the help of in vitro simulated fermentation experiment, fecal samples were collected from the patients with HBV-ACLF and were then cultured in the medium containing different concentrations of Liangxue Jiedu decoction (0, 10%, 50%, and 100%) for 24 hours, and the changes in intestinal flora were analyzed and compared between the HBV-ACLF treatment group, the HBV-ACLF non-treatment group, and the HP group at the genus level. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. Results A total of 10 HBV-ACLF patients were enrolled, with 5 in the HBV-ACLF treatment group and 5 in the HBV-ACLF non-treatment group, and there were 15 individuals in the HP group. Compared with the HP group, the HBV-ACLF non-treatment group had significant reductions in the diversity and abundance of intestinal flora. At the phylum level, Bacteroidetes and Firmicutes were mainly observed in the samples of the HP group, while the HBV-ACLF non-treatment group had a significant reduction in Bacteroidetes and significant increases in Fusobacteria , Proteobacteria , and Fibrobacteres. At the genus level, compared with the HP group, the HBV-ACLF non-treatment group had significant reductions in Ruminococcus, Blautia , and Eubacterium and significant increases in Parabacteroides, Lactobacillus, Fusobacterium , and Streptococcus . The in vitro fermentation experiment showed that compared with the HBV-ACLF non-treatment group, the HBV-ACLF treatment group had significant increases in Ruminococcus, Lachnospira, Bacteroides , and Genusgenus and significant reductions in Fusobacterium and Proteobacteria (all P < 0.05). Conclusion Liangxue Jiedu decoction can regulate intestinal flora disturbance, restore the diversity of intestinal flora, increase dominant bacteria, and reduce pathogenic bacteria, which may be one of its important mechanisms of action in the treatment of HBV-ACLF.

Optimized arterial perfusion strategy in total arch replacement for acute type A aortic dissection with malperfusion syndrome / 中国胸心血管外科临床杂志

@#Objective    To investigate the effect of optimized arterial perfusion strategy on total arch replacement for acute type A aortic dissection (AAAD) with malperfusion syndrome (MPS). Methods    From 2017 to 2019, 51 patients with AAAD and MPS who had received total arch replacement with optimized arterial perfusion strategy in our hospital were included in the optimized perfusion group, including 40 males and 11 females, with an average age of 47.43±13.39 years. A total of 40 patients with AAAD and MPS who had been treated with traditional Sun's surgery were taken as the traditional control group, including 31 males and 9 females, with an average age of 50.66±12.05 years. The perioperative clinical data of the two groups were compared. Results    The preoperative baseline data of the two groups were basically consistent (P>0.05). The comparison of operative data between the optimized perfusion group and the traditional control group showed that in the optimized perfusion group, the extracorporeal circulation time, aortic occlusion time, and circulation-out cerebral perfusion time were significantly less than those in the traditional control group (223.64±65.13 min  vs. 266.77±87.04 min, 114.48±27.28 min vs. 138.20±39.89 min, 8.28±3.81 min vs. 50.53±23.60 min, all P≤0.05). The lowest intraoperative nasopharyngeal temperature in the optimized perfusion group was significantly higher than that in the traditional control group (27.10±1.18℃ vs. 23.6±3.30℃, P=0.000). Postoperative wakefulness time of the optimized perfusion group was earlier than that of the traditional control group (4.50±1.35 h vs. 5.27±1.15 h, P=0.019). The volume of blood transfusions in the optimized perfusion group was significantly less than that in the traditional control group (13.25±9.06 U vs. 16.95±7.53 U, P=0.046). There was no significant difference in ICU time and invasive ventilation time between the two groups (P>0.05). Postoperative complications of the two groups showed that the incidence of postoperative continuous renal replacement therapy in the optimized perfusion group was significantly lower than that in the traditional control group, with a statistically significant difference (21.6% vs. 42.5% P=0.003). The incidence of postoperative delirium, coma, low cardiac row syndrome and limb ischemia in the optimized perfusion group was lower than that in the traditional control group, but the difference was not statistically significant (P>0.05). The incidence of postoperative hemiplegia, sepsis, and secondary thoracotomy in the optimized perfusion group was higher than that in the traditional control group, and the difference was not statistically significant (P>0.05). Postoperative mortality in the optimized perfusion group was significantly lower than that in the traditional control group (13.7% vs. 27.5%), but the difference was not statistically significant (P=0.102). Conclusion    Optimized arterial perfusion strategy and its related comprehensive surgical technique reduce surgical trauma, shorten the operation time, reduce perioperative consumption of blood products. Postoperative wakefulness is rapid and the incidence of complications of nervous system, kidney and limb ischemia is low. Optimized arterial perfusion strategy is suitable for operation of AAAD with MPS by inhibiting the related potential death risk factors to reduce operation mortality.